Porous membranes may be used in a wide variety of applications including filtration technology. The physical and chemical demands on materials used in casting porous membranes can be stringent and difficult to meet. On the one hand it is often desirable to have a membrane comprised of a bulk matrix, e.g. a polymer, which is mechanically strong, thermally stable and chemically inert to most solvents. Typically, polymers meeting these needs will be hydrophobic, although hydrophilic porous membranes, e.g., comprising cellulose, polyamides and the like have been described. Membranes comprised of a hydrophobic bulk matrix will typically have hydrophobic surfaces and thus need to be pre-wetted with an organic solvent in order for most aqueous solutions to pass through. Pre-wetting, however, introduces contaminants, and increases the time and cost of the separation.
Porous membranes are typically used in the separation and purification of complex biomolecules comprised of proteins, peptides, lipids, carbohydrates and the like. These complex biomolecules, tend to interact non-specifically via hydrophobic interactions with the hydrophobic surfaces comprising the porous membranes or via forming ionic or hydrogen bonds with groups on the surface of some hydrophilic membranes, thus resulting in membrane fouling, poor separation and low product yield. Unmodified membranes may thus be poorly suited for many filtration applications involving biological applications. In contrast, hydrophilic membranes comprised of neutral surfaces do not require pre-wetting with an organic solvent and often obviate problems of non-specific hydrophobic or charge-charge interactions between biomolecules and porous membranes encountered during various types of filtration.
One possible approach to the problem of non-specific interactions between biomolecules and porous membranes might be to modify the surface of the bulk matrix comprising porous membranes with a hydrophilic material having a neutral surface. A number of approaches to membrane surface modification have been described to date. These approaches, however, are not without their shortcomings.
One general approach to the problem involves the grafting of a hydrophilic material onto the surface of a porous membrane. Grafting results in a covalently linked coating on the surface of the membrane, see, e.g., U.S. Pat. Nos. 3,253,057; 4,151,225; 4,278,777 and 4,311,573. Grafting may be performed by random oxidation using plasma or corona discharge. This approach may be employed for surface activation of polymer films. Its effects are generally limited due to the limited penetration of active gas species into the porous material.
Grafting may have deleterious effects on the bulk matrix of the porous membrane. The deleterious effects to a membrane introduced by grafting include an increased tendency of the grafted membrane to swell, which in turn may alter the integrity of the membrane and lead to poor permeability.
Another modification technique is the formation of thin cross-linked polymer film on the membrane surface over the course of free radical polymerization of hydrophilic monomers as disclosed in the U.S. Pat. No. 4,618,533. Acrylic-based crosslinkers are typically used.
Methods that teach coating the membrane surface with a mixture of desirable coating molecule and an acrylic cross-linker have been described, see, e.g. U.S. Pat. No. 6,193,077. Also, porous membranes coated with polyethylene glycol (PEG) using argon plasma without an acrylic cross-linker have also been described, see, e.g., Wang et al., 2002, J. Membr. Sci., 195:103. Plasma, however, has limited utility due its inadequate penetration into the porous material.
There are several disadvantages associated with the use of acrylic-based coatings. Included among these are their poor stability towards treatment with a concentrated alkaline solution, a preferred method for cleaning filter assemblies comprising porous membranes. Another disadvantage is that these coatings typically exhibit poor heat stability, thus precluding the use of PEG-based monomers which would make a good protein-repellent surface. Additionally, previously described methods may involve the introduction of trace amounts of carboxylic groups to the membrane, which tend to attract oppositely, charged proteins resulting in non-specific binding to the membrane. Finally, pore plugging remains a problem with many previously described techniques used to modify porous membrane surfaces thus limiting application of this technique.
It would, therefore, be desirable to provide surface modification for porous membranes that overcome the shortcomings described above. In particular, a need exists to provide a porous membrane which does not require prewetting with an organic solvent, and which minimizes non-specific interactions with biomolecules such as proteins and peptides, while at the same time maintaining stability under alkaline conditions typically used to clean membranes. Various embodiments of the invention described herein meet these needs.